Date: 19 Mar 96 00:18:15 EST
From: Mike Darwin <>
Subject: BPI TECH BRIEF #18
Cryopreservation of CryoCare Patient #C-2150
by Mike Darwin
Introduction
On December 12th, 1995 James Gallagher, a 55-year-old
software developer from Sunset Beach, California, became
CryoCare's first member to enter cryopreservation. He also
became the first patient ever to benefit from new
technologies developed to reduce three forms of injury:
* pre-mortem shock
* warm ischemia (the time interval between pronouncement
of death and restoration of adequate blood circulation)
* cold ischemia experienced during initial blood washout
and cooling, and also during iced-transport from the location
where legal death occurred to the facility where
cryoprotective perfusion is carried out.
The following is not quite a full technical report, but
neither is it simply a lay-level of summary of key events
without reference to the technical details and the impact
those details had upon this patient's care and potentially,
future patents' care. It is the aim of this report to
include enough quantitative detail that direct comparisons
can be drawn with previous cases. It can be argued that this
is just *one* patient, that solid inferences or statistical
significance cannot be established with n=1. Generally, this
would be true. However, this patient's course is being
compared with many other animals and humans subjected to
similar protocols.
Using relevant animal models over the last three years,
BioPreservation, Inc. (BPI), the transport and
perfusion/cool-down service provider for this patient, in
conjunction with 21st Century Medicine (21st) has been
evaluating aspects of the protocol used on this patient.
Further, BPI and several of BPI's core technical staff have
had extensive experience applying pre-mortem medication,
transport, and cryoprotective perfusion protocols with
patients from other cryonics organizations in the past, and
also have access to relevant case data from other cryonics
patients whose illness, agonal course, and time to post-
arrest intervention are directly comparable with this
patient's.
At a minimum, we believe that the close correlation of this
patient's response to that observed in the canine experiments using
the same protocol, and especially when contrasted with results
achieved in comparable human cryopreservation patients treated with
previously used protocols (including a patient treated by
BPI; ACS Patient #9577), is significant. Of particular
importance is this patient's core temperature cooling data,
since cooling is constrained by physical laws which are well
understood, and where the predictability and simplicity of
the system used to carry out cooling allows for little
variation from case to case (where patient mass, body fat
content and distribution, and surface area, are comparable,
of course).
The significance of other measured parameters in this
case, such as tissue-specific enzyme release (markers of
ischemic injury for specific organs and for the patient as a
whole) and metabolic parameters, is presently more open to
debate. However, even here we believe that the results
achieved with this patient are so different from that
observed in patients with comparable diagnoses and agonal
courses (and in such close agreement with animal data) that
careful consideration should be given to the results.
Social and Medical Background
The patient first contacted CryoCare (CC) on 15 July,
1995 to inquire about cryopreservation services. He was
familiar with cryonics due to prior association with a
contract worker whom he employed in the early 1980's who was
heavily involved in cryonics. He had also read cryonics
organizations' literature and met with various cryonics
organization members and personnel (where cryonics was a
topic of discussion) again since the early 1980s. The patient
had been in-touch with several cryonics organizations before
contacting CC, after being informed he was terminally ill.
Formal communication with CC administration began by e-
mail on 17 July and Mike Darwin, President of BPI was brought
in for a cryonics consult with the patient on 20 July.
At that time the patient informed BPI that he had been
recently diagnosed with terminal cancer and was interested in
putting cryopreservation arrangements in place. BPI
questioned the patient extensively about his medical history
and treatment and discovered the following relevant
information:
* The patient did not have health insurance and was
paying for medical care piecemeal as crises or problems
occurred.
* The patient had not had a definitive diagnosis of
cancer. After more than five months of sacral pain, the
patient had been CT'ed by his family physician, and the
diagnosis was presumptively based on a single CT scan of the
chest and abdomen which revealed numerous solid lesions which
appeared to be tumor, present in the left kidney and
obliterating the left adrenal gland, and also present in the
caudal lobe of the liver, and possibly the descending colon.
* The patient was seeing an alternative medicine
provider (a biochemist, not a physician) who told him he
probably had primary cancer of the kidney (primary renal
carcinoma) and prescribed a nutrient supplementation regime
coupled with the administration of large doses of urea and
creatinine (waste products of metabolism normally excreted by
the body in the urine) purportedly to stop the spread of the
cancer and convert the cancer cells back to more "normal
morphology." Nutritional supplements of a wide variety but
notably including co-enzyme Q10, vitamin A, beta carotene,
selenium, vitamins E and C, and cesium chloride (13 g/day
cesium chloride ostensibly to stimulate the immune system to
attack and destroy the cancer) were also being administered.
At this time Mike Darwin refused to accept the patient
as a BPI client until a definitive diagnosis of terminal
illness was established. The patient was told that some
moderately to highly treatable cancers such as non-Hodgkin's
lymphoma may appear indistinguishable on CT from other,
untreatable cancers. It was also noted that on the initial
radiology report (which was read to Darwin) that the
radiologist reading the CT remarked on what he felt might be
a mass in the posterior part of the descending colon, but was
unable to tell with certainty due to the presence of feces in
the bowel. The radiologist listed primary adenocarcinoma of
the colon (the most common type of bowel cancer) as the
number one possibility to rule out.
Since the patient did not have health insurance, a
variety of options was discussed to determine the nature and
the treatability of the apparent malignant disease. The
patient was referred to BPI's medical consultant Steven B.
Harris, M.D. and the number of options was rapidly pared
down. If it *was* primary renal carcinoma, the only way to
definitively establish that would be to obtain a sample of
the tumor using CT-guided needle biopsy or to do an "open
biopsy" or lapropscopic biopsy wherein surgery is performed
to open or access a body cavity with a trocar and fiberoptic
scope, to inspect and directly obtain a sample of the
questionable tissue.
Due to the statistically comparatively low likelihood of
primary renal carcinoma in a 55 year-old man (versus the
likelihood of primary adenocarcinoma of the bowel), the
remarks of the radiologist about the possible presence of a
bowel mass on the CT scan, and the absence of health
insurance, it was decided that the most cost-effective and
medically most conservative way to proceed would be to have
the patient undergo fiberoptic colonoscopy (direct
visualization with a flexible fiberoptic viewing device) of
the colon and look to see if there was any tumor present.
(Common things are common; metaphorically the CT was the
equivalent of loud hoof beats in the distance, and when one
hears hoof beats in the Western United States one generally
thinks of horses, not zebras. In this case horses = primary
adenocarcinoma of the bowel).
A few days later the colonoscopy was performed and our
suspicions were confirmed; there was a large mass nearly
obstructing the descending colon which appeared on visual
inspection to be a malignancy.
Dr. Harris and Mike Darwin both advised the patient that
bowel obstruction by the rapidly growing tumor was imminent
and that he should consider a palliative colostomy. The
patient was resistant to doing this for several reasons.
First, he had considerable confidence that enemas with urea,
and his alternative cancer treatment regime would at least
shrink the tumor (he was receiving considerable encouragement
from his alternative care provider in this regard), so that
surgery could be avoided. Secondly, the anticipated cost of
a colostomy and associated care would jeopardize the funding
the patient had set aside from his savings for
cryopreservation.
This created a new and difficult ethical problem for
both BPI and CC. Clearly CC needed to maintain its funding
minimums at a level sufficient to provide reasonable safety
margins for continued cryogenic care of the patient. And,
clearly, BPI is not in the charity business and has staff to
pay and marginal costs to address. On the other hand, it is
hardly tenable to confront a patient with the choice between
foregoing cryopreservation or facing a gruesome and agonizing
death from an obstructed bowel (months earlier than would be
the case if colostomy or colectomy were performed)
Since this patient was low on funds already (nearly
$50,000 of savings having been spent on piecemeal alternative
"medical" care) he had already agreed to the use of new
procedures and to the biopsying of his brain in exchange for
reducing the basic cost of BPI's procedures. Confronted with
this new situation, BPI reduced its charge to below the
break-even level and the patient volunteered to cooperate
with what then constituted extraordinary antemortem
monitoring.
This was the first time BPI, CC, or, to our knowledge,
any cryonics organization has been faced with a situation
where a patient (and his cryonics organizations) was
confronted with a choice between reasonable standard of care
(avoiding a serious, life shortening, and definitely quality-
of-life reducing complication of the illness), and being
cryopreserved. This was deeply disturbing for all involved,
and merits intense discussion in the immediate future, not
just by CC and BPI, but by the cryonics community as a whole.
While it is inappropriate to belabor this point here, this
case points up that increasingly cryonics organizations will
be dealing with both members and non-members who have no
health insurance (not even HMO coverage), no access to
government healthcare such Medicaid, Medicare or VA care,
and/or who have limited access to health care with HMO, PSO,
PPO or other care which forces them to make major quality of
life or length of life decisions based on use of their non-
healthcare allocated funds such as savings, property equity,
and even accumulated cash value or resale value of life
insurance policies--including those specifically earmarked
for cryonics.
Further, in some cases the state, acting through the
courts, may appropriate these assets at the request of
guardians or relatives. The issues raised by the
inevitability of a massive restructuring of health care cost
and availability in the United States which is occurring now,
should be considered now. This case should serve as a
sentinel in this respect.
A few days after his colonoscopy, the patient began to
experience symptoms of bowel obstruction (increased anorexia,
nausea, shot-gun pellet stool, vomiting and abdominal
distention), and so a double-barreled colostomy was performed
on 29 July. This procedure was uneventful and the patient
returned home where he was cared for by his sister, his
brother-in-law and his nephew. The patient continued with
his alternative medicine regime, although, due to increasing
nausea, he abandoned use of the cesium chloride.
At this point BPI became disengaged from close
involvement with the case over issues related to funding
details. This was an issue between the patient and CC, and
until the patient became a fully signed-up CC
cryopreservation member, it was inappropriate for BPI to be
as closely involved.
As financial negotiations proceeded favorably, BPI again
became involved and made a home visit on 15 October with
medical advisor Dr. Harris and BPI staff members Carlotta
Pengelley, LVN, Joan O'Farrell, Sandra Russell, and Mike
Darwin also present. The purpose of this visit was to
evaluate the home for logistics of access (it was a second-
story apartment with outside stair-access only) and equipment
set-up, meet the family and prepare them for the reality of
transport, assure the patient's medical and pain control
needs were being met, encourage the patient to enroll in home
hospice, and to carefully medically examine the patient in
order to determine "staging" or likely time-course to legal
death for cryonics reasons.
Dr. Harris examined the patient thoroughly during this
visit and baseline blood chemistries were drawn, including
samples collected, spun-down and frozen to dry ice
temperature on-site for subsequent baseline antioxidant and
lactate levels (the former to be done by Pantox Labs of San
Diego, CA) as well as for a routine chemistry panel an a
screening for infectious diseases.
During this visit Dr. Harris noted that the patient had
right leg weakness (barely noticeable) a right visual field
cut (right homonymous hemianopia), nausea and anorexia (lack
of appetite) and that he weighed 73.1 kg down from a previous
healthy weight of 86-88 kg. Careful history taking also
disclosed recent (2 weeks duration) inability to read, which
the patient attributed to lack of ability to concentrate, and
urinary incontinence. The patient was noted to have cancer
wasting syndrome and complained of severe back pain of eight
months duration. Further, Dr. Harris felt it very likely the
now nearly immobilizing back pain (the patient was
constrained to lie face down on a specially modified cot most
of the time) was due to involvement of the sacrum with
metastatic disease.
Dr. Harris' presumptive diagnoses at the conclusion of
the home visit were probable large metastases (4-6 cm) of the
primary colon cancer to the left occipital lobe of the brain
which was likely responsible for the right-sided visual field
cut, weakness, and incontinence. Probable metastatic
involvement of the sacrum was assumed, with resulting
uncontrolled bone pain. Further presumptive diagnoses were
tumor necrosis factor (TNF) and related cytokine cancer
wasting syndrome, and poor nutritional status (calorie count
estimated at 1500 kcal/day or less). The family was urged to
take the patient to an imaging center and have an MRI or CT
of the head done to rule out malignant involvement of the
brain (the patient's family was informed of the high
probability of the metastasis, but the patient at this time
was not).
A CT scan with and without contrast was performed on 17
October and a 6cm mass was indeed found in the left occipital
lobe of the brain. Dr. Harris, in conjunction with the
patient's newly acquired primary care physician persuaded the
patient that it was imperative that he undergo palliative
radiotherapy to his head and to his sacrum (lower back). The
patient was resistant to undergoing this treatment because of
his disdain for "radiation treatment of cancer" and because
of his concerns about possible damage to his brain from the
radiation which might compromise his chances for good
cryopreservation.
Dr. Harris was instrumental in convincing the patient to
get palliative radiation treatment. He explained that
failure to do so would result in hemiplegia (paralysis on one
side) possible loss of speech, complete incontinence of
bladder and stool, and likely death from elevated
intracranial pressure which might very likely expose his
higher brain to extended periods of periods of minimal or
absent blood flow (ischemia) for hours prior to cardio-
respiratory arrest and pronouncement of legal death. The
consequences of unchecked growth of an aggressive malignant
tumor in the brain, versus the by comparison trivial effect
of palliative radiotherapy (increased sleepiness and
fatigue, hair loss and modest compromise of short-term
memory) were emphasized.
(In cases of metastatic brain disease the entire brain
is usually radiated both to hold down the costs associated
with shielding and selective irradiation of the tumor, and,
more importantly, to "head off" the proliferation of other
metastases; where you see one seed sprouting there are likely
other to be others germinating. Whole brain irradiation
decreases the likelihood of secondary tumors developing in a
patient who is terminal with aggressive malignant disease).
The patient had previously been scheduled to have a
chronic intrathecal line placed into his lumbar spine for
delivery of chronic intrathecal morphine by pump for chronic
pain control, and on 16 October, this was done. Within 48
hours, however, the patient was unable to walk, and was
admitted to the hospital. There, neurological exam showed
profound bilateral leg weakness and normal spinal fluid. X-
rays also showed a metastatic lytic lesion to the right
sacrum, with possible nerve compression to the right leg.
The neurologist examining the patient for the first time
thought that the new weakness was due to cauda-equina
compression syndrome from tumor; and rejected the idea, put
forth by Dr. Harris, that the very rapid onset of weakness
coupled with the relationship to the intrathecal line
placement, made that procedure suspect. Dr. Harris, however,
was able to convince the patient's primary physician of this
possibility, and the intrathecal morphine was discontinued.
Within a day the patient recovered use of his legs, but a
definitive diagnosis of the problem was never made. He
continued for the rest of his course, however, on morphine
delivered via peripheral line.
During hospitalization for the leg problem, the patient
was seen by a radiotherapist, and radiotreatment to his brain
and sacrum was initiated. In particular, he underwent 10
fractionated doses of palliative radiotherapy to his head,
with 4,000 rads (cGy) to the whole brain and a 10,000 rad
boost to the tumor.
The patient was also enrolled in a good Home Hospice
program which did much to help the family by providing basic
care advice and improved pain management.
Financial negotiations between the patient, the
patient's representative family member and CC continued (with
some last-minute input from BPI) and the patient became a
fully funded CC cryopreservation member on 7 November, 1995.
On 5 November the patient spoke with Dr. Harris by phone
and reported himself as being very depressed and wishing to
withdraw from the program of anti-TNF and immune stimulating
drugs the patient had been started on after the withdrawal of
the alternative medicine practitioner. Dr. Harris noted that
the patient sounded sort of breath (dyspneic) on the phone
and asked the patient if he was, which the patient denied.
That evening the patient was transported to the
emergency department (ED) of a nearby hospital acutely short
of breath and panicky with air hunger. The paramedics who
carried out the transport noted that the patient had
diminished breath sounds on the right side nearly to the base
of the right lung, and began oxygen at 2 liters per minute
(LPM) during transport. When the patient was examined in the
ED the ED physician said he could find no diminished breath
sounds, stopped the oxygen, waited "a few minutes," noted the
patient's oxygen saturation by pulse oximetry was 96%, and
told him to go home. At that point Dr. Harris spoke with the
ED physician and requested that arterial blood gases be drawn
and a chest X-ray be taken. This was a medically sound
request for several reasons: first, it would help establish
the basis of the patient's shortness of breath and determine
if palliative oxygen therapy should be considered to reduce
or eliminate "air hunger." Or, failing relief of air hunger
with oxygen supplementation, increase the degree of sedation
to make the patient more comfortable. Second, from a cryonics
standpoint it was important to know if the patient was
experiencing a complication or exacerbation of the primary
disease (such as pneumonia; a big risk here since the brain
tumor required immunosuppressively high doses of
dexamethasone to control intracranial pressure) which would
justify deployment of the standby team.
The ED physician politely but firmly brushed off Dr. Harris'
request (even though the patient was willing to pay for the
requested tests in cash) and sent the patient home. During the
trip home the patient again became acutely dyspneic and spent the
night miserable and panicky with air hunger.
The next morning the patient's HMO waiting period was up
(he had HMO coverage available regardless of pre-existing
illness, but only after a waiting period) and the patient was
again transported by ambulance, this time to the office of
the internist employed by the HMO. The physician lifted the
blanket, looked at the patient, informed the patient that
"pneumonia was the cancer patient's friend," further informed
the patient that he had end-stage cancer, and sent the
patient home, *again without oxygen*. At this point Dr.
Harris intervened and arranged for palliative oxygen therapy
in conjunction with the patient's private physician.
The following weeks saw an up and down course for the
patient. The radiotherapy restored his vision and ability to
work initially, and he experienced much less bone pain.
(Prior to this time the patient had worked as a consulting
programmer on a part-time basis as his illness had
permitted.) However, he continued to lose weight and
eventually began to experience intermittent but progressive
dyspnea, constant nausea with occasional vomiting, and
exogenous depression associated with clearly deteriorating
quality of life. Finally, he became unable to work once
again. The patient was now receiving more or less continuous
IV morphine administered peripherally through a strap-on
battery-operated pump.
The day after Thanksgiving, 24 November, a second home
visit by BPI staff (without Dr. Harris) was carried out for
the purpose of collecting baseline cerebral functioning
monitoring (CFM) data and evaluating the patient's condition
first hand. The patient was noted to appear slightly more
wasted, to be largely oxygen dependent, but to have well
managed pain and to be ambulatory for hygiene, and limited
socialization. Baseline EKG and CFM data were collected and
the patient's feelings and thoughts about cryopreservation,
and his informed consent were videotaped.
An unfortunate and unexpected sequelae to this visit was
that one of the BPI team members was infected with influenza
A and unaware of it at the time of the visit. Within 48 hours
of the visit the patient was febrile (39 degrees C), severely
dyspneic, and suffering profound malaise and myalgia. The
patient called BPI to report he was ill and the hospice nurse
was called in to evaluate breath sounds and consult with
BPI's medical advisor (Harris). The hospice nurse reported no
change in breath sounds, no cough and no evidence of
pneumonia, but rather a febrile illness with myalgia
consistent with the flu.
It was explained to the patient that he probably had
early influenza (onset of symptoms was that AM) and that this
could probably be treated with combination anti viral drugs
and an antibiotic to protect against secondary infection.
Alternatively, the patient was told he could elect to refuse
treatment which would carry with it the likelihood of death
from pneumonia or some other inter-current infection. These
choices were reviewed with the patient because of the
patient's prior, repeatedly stated desire to refuse further
life-extending care, including refusal to see a pulmonologist
and oncologist to evaluate the cause of the dyspnea and
perhaps treat it, if it was secondary to tumor-related
compression of a large bronchus. (Such treatment can be
simply carried out with additional localized radiotherapy, or
even laser ablation of tumor growing into a bronchus.)
The patient decided to accept treatment for the
influenza infection and was started on p.o. (oral) ribavirin
400 mg q. 8 hours, and 100 mg b.i.d. rimantidine, an
antiviral specific for influenza A. Antibiotic prophylaxis
for secondary infection was instituted with doxycycline 100
mg b.i.d.
There was prompt improvement in symptoms and signs of
the illness with the patient becoming afebrile in less than
24 hours from the start of treatment with antivirals and
antibiotic.
During the closing days of November the patient
experienced the typical interleaving of relatively "good"
days with progressively worse and more frequent "bad " days.
The patient's p.o. medications at this time were:
aspirin 1.25 grain, p.o., daily
co-enzyme Q10, 100 mg p.o. t.i.d.
dexamethasone, 4 mg t.i.d.
doxycycline, 100 mg, b.i.d.
d-alpha tocopherol, 1,000 I.U., t.i.d.
ascorbic acid, 1 g t.i.d.
phenytoin (Parke Davis), 300 mg q.d.
morphine sulfate by IV pump p.r.n. for pain.
50 mg thalidomide, p.o. before retiring
10 mg melatonin, p.o. before retiring
END OF PART OF BPI TECH BRIEF #18